The overall objective of this research is to describe the relationship of DNA metabolism and the process of aging. In particular, we wish to evaluate the possible deterioration of DNA function as a precedent or concomitant of the aging process. We will conclude several studies concerning indicators of DNA function in cultured cells with relevance to aging: (1) patterns of removal of sites sensitive to exogenous endonucleases; (2) cellular mediation of chromatin rearrangements; and (3) intrinsically induced sister chromatid exchanges. In view of our emerging conclusions from these studies where senescence of diploid cells in vitro probably has no relationship to cell aging in vivo, more relevant in vivo studies are being initiated; studies including the use of body fluids and tissues from human beings so that possible indices of aging can be compared to rodent or rabbit species. The observation that a hypersensitive state in cells is induced by a mutagen possibly relating to the aging process will be pursued by examining stressed cellular populations compared to normal populations in vivo through the lifespan of an organism. We will examine discrete cellular events versus entire populations of events in tissues to determine if the hypersensitive state in growing numbers of cells in an aging animal could be an underlying mechanism for aging. The direct comparisons between human beings and rodent species will begin to answer questions concerning inter-species variations of aging and the difference in lifespans of different species.